International Scholarly Research Network ISRN Pharmacology Volume 2012, Article ID 478023, 7 pages doi:10.5402/2012/478023

Research Article Beneficial Effects of Pentanema vestitum Linn. Whole on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits

Ikram Ilahi,1 Ali Asghar,2 Shujat Ali,2 Murad Khan,3 and Nasrullah Khan2

1 Department of Zoology, University of Malakand, Chakdara, Dir Lower 25000, Khyber Pakhtunkhwa, 2 Department of Botany, University of Malakand, Chakdara, Dir Lower 25000, Khyber Pakhtunkhwa, Pakistan 3 Department of Biotechnology, University of Malakand, Chakdara, Dir Lower 25000, Khyber Pakhtunkhwa, Pakistan

Correspondence should be addressed to Nasrullah Khan, [email protected]

Received 9 August 2012; Accepted 12 September 2012

Academic Editors: F. J. Miranda, T. B. Vree, and S.-N. Wu

Copyright © 2012 Ikram Ilahi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P<0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P<0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits.

1. Introduction diabetes is high ranging from 7.6 to 11% [3, 4]. More than 230 million people globally are affected by the disease [5]. Diabetes mellitus is a group of metabolic diseases charac- Diabetes mellitus is treated by different allopathic medi- terized by hyperglycemia resulting from defects in insulin cines. Insulin-dependent diabetes mellitus is treated by sub- secretion, insulin action, or both. The type of diabetes that cutaneous administration of exogenous insulin. Non-insu- occurs due to the loss of insulin producing beta cells of the lin-dependent diabetes is treated by oral hypoglycemic drugs. islets of Langerhans in the pancreas is called type 1 or ThetwomajorgroupsoforalhypoglycemicdrugsareSul- insulin-dependent diabetes mellitus (IDDM) and the type of phonylureas and biguanides. Sulphonylureas act by stimu- diabetes which is due to insulin resistance or reduced insulin lating insulin release from beta cells and also by promoting sensitivity is called type 2 or non-insulin-dependent diabetes its action through other mechanism. The common Sulpho- mellitus (NIDDM). nylureas are Tolbutamide, Tolazamide, Glibenclamide, Glip- The diabetic patients manifest the classic signs and symp- izide, and Glimepiride. Biguanides exert their action by toms of chronic hyperglycemia (polydipsia, polyuria, blurred decreasing gluconeogenesis and increasing the peripheral vision, headaches, and rapid weight loss), sometimes accom- glucose consumption. The marketed Biguanides is Metfor- panied by nausea and vomiting [1]. Hyperglycemia is asso- min [6]. ciated with an alteration in lipid parameters which leads to Management of diabetes is a huge burden. Currently cardiovascular complications [2]. The incidence of diabetes available antidiabetic pharmacological agents have several is increasing worldwide. In Pakistan the prevalence of complications which stimulated the researchers to explore 2 ISRN Pharmacology novel antidiabetic agents with different mechanism of action was repeated for three times, and the combine filtrate was [7]. It is hypothesized that the ultimate therapy for type I then evaporated on a rotary evaporator Heidolph Laborota and type II diabetes lies in the herbal approach [5]. There are 4000 efficient (Germany) under reduced pressure and ob- many online published reports on the usefulness of medici- tained a thick solution. This extract in thick solution form nal in the treatment of diabetes. was transferred to a beaker and placed in a well-ventilated Pakistan is rich in medicinal plants [8]. Some of them room for three days for evaporating the remaining solvent, have been reported for their antidiabetic actions. These and finally a thick paste of crude extract of grayish color was include Adhatoda vasica, Ficus benghalensis, Psidium guajava, obtained, yielding approximately 78 grams (13% w/w). Momordicacharantia,Cajanuscajan,Vignamungo,Allium cepa, Zizyphus jujuba, Dodonaea viscosa, Ocimum sanctum, 2.3. Preliminary Phytochemical Screening. A preliminary Momordica charantia, Trigonella foenum-graecum, Solanum phytochemical screening of 70% methanol extract of Pen- nigrum, Vigna sinensis, and Withania somnifera [9]. tanema vestitum whole plant was carried out by using stan- Many medicinal plants are used in folkloric medicines dard procedures [17]. for the management of diabetes, at individual or community levels in various parts of Pakistan. Several of these plants have 2.4. Animal Used. Fifty-six male rabbits of Oryctolagus cuni- not been screened or reported for their antidiabetic property. culus species weighing 1200–1500 grams and 4–6 months of The plant Pentanema vestitum Linn. is one of the medicinal age were purchased from local market. They were housed in plants found in some parts of Malakand division, khyber one of wide chambers of Bio Park at University of Malakand, Pakhtunkhwa, Pakistan. It belongs to the family Khyber Pakhtunkhwa, Pakistan. The rabbits were fed on and Pentanema. It grows wild at 400–1500 m height green grasses and allowed tape water ad libitum. They were fromsealevel.ThePentanema vestitum has tap root system; acclimatized for 30 days before starting experiment. up to some extent, the branched root system is also present. The stem is erect, branched and herbaceous in nature; the leaf is exstipulate, serrate entire and oblong. The inflorescence is 2.5. Acute Toxicity Studies. The acute toxicity test of the capitulating or capitula and radially arranged in the form of extract was performed according to the OECD guidelines loose corymbs [10]. The residence in some parts of Malakand no. 420. A total of 20 male rabbits were used for this test. division, use the dry powder of whole plant of Pentanema The rabbits were divided into four groups, 5 rabbits in each vestitum for the treatment of asthma and diabetes. The plant group. The four groups of rabbits were orally administered Tridax procumbens that belong to the family Asteracea to with various doses of the extract ranging from 1000 to which Pentanema vestitum belong has been reported for anti- 2500 mg/Kg body weight. The animals were monitored for hyperglycemic activity [11, 12]. The antidiabetic property two weeks for mortality and behavioral, neurological, and of medicinal plants is attributed to their possession of autonomic responses. No death occurred and also no abnor- phytochemical ingredients that is, tannins, saponins, gly- malities were detected in behavioral, neurological and auto- cosides, flavonoids, and phenols [13–16]. Therefore during nomic responses till the end of second week. The extract was the present work, initially Pentanema vestitum extract was found to be safe up to the dose of 2500 mg/Kg body weight. subjected to phytochemical screening for investigating the In the present study the extract dose of 600 mg/Kg body presence of anti-hyperglycemic ingredients and in the next weight was chosen during the study of glucose-induced steps the extract was orally administered to glucose induced hyperglycemic rabbits and the extract dose of 100 mg/Kg nondiabetic hyperglycemic rabbits and alloxan-induced dia- body weight during the study of alloxan-induced diabetic betic rabbits. The objective of the study was to confirm the rabbits. antidiabetic activity of the plant Pentanema vestitum and also to assess its beneficial effects on other biochemical parame- 2.6. Experimental Design. The research work was divided ters of alloxan-induced diabetic rabbit models. into two phases. During the first phase, the anti-hyper- glycemic property of plant extract was tested in glucose- induced nondiabetic hyperglycemic rabbits. The second 2. Materials and Methods phase involved the study of effects of plant extract on the serum levels of glucose, GPT, ALP, bilirubin and creatinine 2.1. Plant Material. The whole plant of Pentanema vestitum of alloxan-induced diabetic rabbits. Linn. was collected from the campus of University of Mal- akand, Khyber Pakhtunkhwa, Pakistan. The plant was iden- 2.7. Details of the First Phase. A total of 15 rabbits were used tified by Mr. Mehboob ur Rahman, Assistant professor, during this phase. The rabbits were divided into control, Department of Botany, Government Postgraduate Jahanzeb standard and extract-treated groups. Pretreatment (0 hour) College Swat Khyber Pakhtunkhwa, Pakistan. blood glucose levels of all the rabbits were measured after a 17-hours fast. Then, the control group was orally admin- 2.2. Preparation of Crude Extract. The plant was cleaned, istered with 2% DMSO solution (3 mL/kg body weight), shade dried, and coarsely ground. The powder material in standard group with glibenclamide (0.2 mg/kg body weight) the amount of 600 grams was soaked in 5000 mL of 70% dissolved in 3 mL of 2% DMS solution, and extract-treated methanol for 3 days with occasional shaking. The soaked group with Pentanema vestitum extract (600 mg/kg body materials was filtered through muslin cloth. This procedure weight) in 3 mL of 2% DMSO solution. After 30 minutes of ISRN Pharmacology 3 drug and extract administration, all the rabbits were orally 2.12. Chemical/Kits and Equipment Used during Experiment. administered with glucose at the dose of 2 g/kg body weight. Alloxan monohydrate (Applichem, Germany), glucose kit Bloodglucoselevelsweremeasuredthroughanelectronic (Biomega, Germany), cholesterol (Lab Test, Brazil), triglyc- glucometer (Accu check Advantage Π, Roche Diagnostics, eride (Biomega Laboratories, Holzheim, Germany), LDL Germany) with a single drop of blood from marginal vein of (Thermo Scientific, USA), HDL kit (Thermo Scientific, rabbit ear after 1/2, 1, 2, and 3 hour, of glucose load. USA), GPT kit (FAR srl Italy), ALP kit (Dia sys International, Germany), bilirubin liquicolor (Human, Germany), and cre- atinine kit (Chromatest, Spain). For the estimation of all the 2.8. Details of the Second Phase. During the second phase serum parameters, UV spectrophotometer (1700 Shimadzu of experiment a total of 21 alloxan-induced diabetic rabbits Japan) was used. were divided into three groups, namely, diabetic control, standard and extract groups (7 rabbits each). The rabbits of control group received only 2% DMSO in amount of 2.13. Statistical Analysis. Results are presented as means ± 2 mL/kg body weight per oral, standard group received standard deviation/standard error of means. The data of the glibenclamide at a dose of 0.2 mg/kg body weight per oral first phase of experiments was subjected to Duncan, test, and per day in 2 mL of 2% DMSO solution and extract group the data of second phase of experiments was analyzed by received Pentanema vestitum extract at a dose of 100 mg/kg Dunnett, Test of Post Hoc Multiple comparison in One Way body weight/oral/day in 2 mL of 2% DMSO solution. The ANOVA. For these analysis, computers software SPSS 16.0 duration of the treatment was 28 days. was used.

2.9. Induction of Diabetes. Before induction of diabetes base- 3. Results line serum glucose, cholesterol, triglyceride, LDL, HDL, GPT, 3.1. Preliminary Phytochemical Studies and Acute Toxicity ALP, bilirubin, and creatinine estimation was done. Then Studies. The Preliminary Phytochemical studies of 70% a 3 mL solution of 100 mg alloxan monohydrate for per methanol extract of Pentanema vestitum whole plant revealed kilogrambodyweightofeachrabbitwaspreparedin0.9% the presence of tannins, saponins, glycosides, flavonoids and saline. Three-milliliter solution of 100 mg alloxan for per kg phenols. The acute toxicity studies showed that the extract is body weight was injected into the peritoneal cavity of each safe up to the dose of 2500 mg/kg body weight in rabbits. rabbit for 3 consecutive days. Before the injection of alloxan, the rabbits were given 12 hour fasting. Each day, each rabbit was orally given 2 mL solution of 500 mg glucose prepared in 3.2. Results of the First Phase of Experiments. During the first ff distilled water. After 24 hours of each alloxan injection, the phase of the present research, the anti-hyperglycemic e ect blood glucose was regularly estimated through an electronic of 70% methanol extracts of Pentenema vestitum whole plant glucometer (Accu check Advantage Π, Roche Diagnostics, was studied in glucose-induced nondiabetic hyperglycemic Germany) with a single drop of blood from marginal vein rabbits (Figure 1). During this study, at zero hour, there was ff of rabbit ear. The rabbits with glucose level above 200 mg/dL no significant di erence in the blood glucose levels of all P> . were considered diabetic and included in the experiment. groups ( 0 05). After 1/2 hour of glucose load, there occurred extensive increase in the glucose levels of all the groups, however the mean glucose levels of the glibenclamide 2.10. Dosing Procedure. A 400 mL solution of 20 grams of (305.2 ± 9.1 mg/dL) and the Pentenema vestitum extract- 70% methanol crude extract of Pentanema vestitum was treated groups (294.2 ± 16.09 mg/dL) were non-significantly prepared in 2% DMSO solution. Each mL of the solution was (P>0.05) lower than the glucose-loaded control group containing 50 mg of extract. Each rabbit of extract-treated (318.5 ± 18.12 mg/dL). After the 2nd hour of glucose load group was orally administered with extract solution in the level of glucose declined in all the groups in response to amount of 2 mL/kg body weight per day. For standard group time. The mean glucose level of the glibenclamide (149 ± each day 2 mg of glibenclamide was dissolved in 20 mL dis- 11.4 mg/dL) and the extract-treated group (126.2 ± 6.2 mg/ tilled water. Each mL of the solution was containing 0.1 mg dL) was lower than that of the hyperglycemic control group of glibenclamide. Each rabbit of standard group was orally (182.5 ± 1.7 mg/dL), and this time the difference was signifi- receiving 2 mL of glibenclamide solution which was contain- cant (P>0.05). The plant extract and the drug glibenclamide ing 0.2 mg of glibenclamide for 1 kg body weight per day. For were statistically homogeneous in antihyperglycemic activity all oral administrations, esophageal catheter was used. (P>0.05). After 3rd hour of glucose load the drug and the extract were still showing glucose-lowering activity. The 2.11. Collection of Blood and Isolation of Serum. After 28 days blood glucose level of the drug (93 ± 11.95 mg/dL) and the . ± . of treatment 3 mL of blood was collected from lateral saphe- extract-treated group (114 2 12 91) was significantly lower nous vein of each rabbit using syringe with 23GX1 gauge than the hyperglycemic control group (135 ± 6.21 mg/dL) P> . needle. Blood obtained from the lateral saphenous vein of ( 0 05). This time also the drug and the extract showed ff P> . each rabbit into a falcon tube was allowed to clot. Serum similar anti hyperglycemic e ect ( 0 05). samples were obtained by centrifuging the clotted blood samples at 4500 rpm for 5 minutes, using Eppendorf Cen- 3.3. Results of the 2nd Phase of Experiments. During the sec- trifuge 5702R. ond phase of experiment the diabetic rabbits showed high 4 ISRN Pharmacology

450 Table 1: Serum parameters of rabbits before and after induction of N = 400 a diabetes ( 7). a 350 b After diabetes a a b Parameters Before diabetes 300 (diabetic control) 250.1 ± 7.8 250 Glucose (mg/dL) 103.57 ± 5.1 (+141.47%) 200 a b 46.6 ± 6.3 a Cholesterol (mg/dL) 15.3 ± 4.6 150 a a a b b (+204.57%) Glucose level (mg/dL) level Glucose b 100 81.7 ± 10.9 Triglyceride (mg/dL) 33.9 ± 3.1 50 (+141%) 0 39.2 ± 7.5 LDL (mg/dL) 10.9 ± 2.4 0 hr1/2 hr 1 hr 2 hrs 3 hrs (+259.6%) Hours 14.1 ± 5.6 HDL (mg/dL) 27.0 ± 3.2 (−47.77%) Control 76.71 ± 4.29 Standard GPT (U/L) 11.7 ± 3.5 Extract (+555.64%) 51.14 ± 3.26 ALP (U/L) 9 ± 1.5 Figure 1: The effect of 70% methanol extract of Pentanema vesti- (+468.2%) tum whole plant on the blood glucose level of glucose-induced 2.23 ± 0.14 Bilirubin (mg/dL) 0.5 ± 0.1 nondiabetic hyperglycemic rabbits. Values are means and standard (+364%) deviation of 5 replicates. Mean sharing a letter in common are not 2.08 ± 0.9 significantly different at P<0.05. Means sharing no letter in Creatinine (mg/dL) 0.45 ± 0.01 (+362.2%) common are significantly different at P<0.05. Values are means and standard error of means (SEM) of 7 replicates. Values in parentheses indicate percent increase (+) or decrease (−) in parameters of diabetic animals from normal baseline values. level of serum glucose, cholesterol, triglyceride, LDL, GPT, ALP, bilirubin, creatinine and low level of HDL (Table 1). 4. Discussion The effects of 70% methanol extract of Pentenema vestitum on these parameters have been shown in Table 2. During The preliminary phytochemical studies of 70% methanol the assessment of serum glucose, the Pentenema vestitum extract of Pentanema vestitum whole plant revealed the pres- extract and the standard reference drug glibenclamide caused ence of tannins, saponins, glycosides, flavonoids and phe- 18.95% and 13.43% reduction, respectively. The difference nols. These ingredients have been reported for their anti- from diabetic control was significant (P<0.05). hyperglycemic activity [13, 14]. During the study of lipid profile, there occurred signifi- In the present study, during the first phase of experi- cant reduction in the serum levels of cholesterol, triglycerides ments, 70% methanol extract of Pentanema vestitum whole and low density lipoprotein (LDL) both in the extract- and plant showed anti-hyperglycemic property in glucose-in- drug-treated groups as compared to diabetic control (P< duced nondiabetic hyperglycemic rabbits. During this study, 0.05). The observed effects with extract were more pro- initially glucose level remarkably elevated in all groups but nounced than the drug glibenclamide. Extract caused 58.5% after two hours of glucose administration there occurred a reduction in cholesterol, 46.14% in TG and 57.90% reduc- decline in glucose level of all groups. Pancreas is the primary tion in LDL. Whereas glibenclamide caused 34.54% reduc- organ involved in sensing the organism’s dietary and ener- tion in cholesterol, 26.07% in TG and 26.02% reduction in getic states via glucose concentration in the blood and in LDL. The Pentanema vestitum extract and the reference drug response to elevated blood glucose, insulin is secreted [18]. glibenclamide showed a different effect on serum high den- In conditions of high blood glucose level, oxidative meta- sity lipoproteins (HDL) than on other lipids. The serum bolism is increased in pancreatic β-cells which results into HDL levels were significantly elevated both in extract (90%) increased ATP production in mitochondria [19–21]. The and glibenclamide (60.99%) treated groups as compared to increase in intracellular ATP closes the ATP-sensitive K+ + diabetic control group (P<0.05). channels (KATP ), decreasing the hyperpolarizing outward K During the study of serum levels of GPT, ALP, bilirubin flux. This results in depolarization of the plasma membrane and creatinine the standard drug glibenclamide caused and influx of extracellular Ca2+ through the voltage-gated 29.05% reduction in serum GPT, 24.12% in ALP, 25.32% in Ca2+ channels. The increase in intracellular Ca2+,activates bilirubin and 34.61% reduction in creatinine. The effects of protein motors and kinases, which then mediate exocytosis Pentanema vestitum extract on these parameters were more of insulin-containing vesicles which lead to increased insulin pronounced which caused 55.67% reduction in serum GPT, and decreased blood glucose levels [22]. 61.28% in ALP, 61.28% in bilirubin and 40.38% reduction in In the extract- and drug-treated groups of rabbits the creatinine. The mean levels of these parameters in the ani- glucose level was found significantly lower as compared to mals of extract- and drug-treated group were significantly the control group, representing the supportive action of lower as compared to the diabetic control group (P<0.05). extract and drug glibenclamide in glucose utilization. The ISRN Pharmacology 5

Table 2: Biochemical parameters of alloxan-induced diabetic rabbits after 28 days treatment with drug and P. vestitum extract (N = 7).

Parameters Diabetic control Std Pv ext 216.5 ± 4.7∗ 202.7 ± 7.7∗ Glucose (mg/dL) 250.1 ± 7.8 (−13.43%) (−18.95%) 30.5 ± 7.3∗ 19.3 ± 7.3∗ Cholesterol (mg/dL) 46.6 ± 6.3 (−34.5%) (−58.5%) 60.4 ± 8.2∗ 44.0 ± 6.5∗ Triglyceride (mg/dL) 81.7 ± 10.9 (−26.07%) (−46.14%) 29.0 ± 3.8∗ 16.5 ± 5.8∗ LDL (mg/dL) 39.2 ± 7.5 (−26.02%) (−57.90%) 22.7 ± 5.4∗ 26.8 ± 5.6∗ HDL (mg/dL) 14.1 ± 5.6 (+60.99%) (−90.07%) 54.42 ± 2.09∗ 34.0 ± 2.7∗ GPT (U/L) 76.71 ± 4.29 (−29.05%) (−55.67%) 38.8 ± 3.4∗ 19.8 ± 3.2∗ ALP (U/L) 51.14 ± 3.26 (−24.12%) (−61.28%) 1.74 ± 0.09∗ 1.03 ± 0.15∗ Bilirubin (mg/dL) 2.23 ± 0.14 (−25.32%) (−55.7%) 1.36 ± 0.6∗ 1.24 ± 0.5∗ Creatinine (mg/dL) 2.08 ± 0.9 (−34.61%) (−40.38%) Std: standard glibenclamide group and Pv ext: P. vestitum extract group. Values are means and standard error of means of 7 replicates. ∗The mean difference is significant at P<0.05 level. Values in parentheses indicate percent changes from the diabetic control group. anti-hyperglycemic effect of glibenclamide during oral glu- range from hypercholesterolemia to hyperlipoproteinemia is cose tolerance test has been attributed to enhance activity one of the many modifiable risk factors for coronary artery of beta cells of pancreas resulting in secretion of large diseases, stroke, and peripheral vascular disease [28]. During amount of insulin [23]. Mechanism behind the anti-hy- the present study, the reduction in serum glucose level of perglycemic activity of the extract may involve insulin like extract-treated diabetic rabbits was accompanied by marked action by increasing peripheral glucose consumption, or it reduction in the serum levels of cholesterol, triglyceride and may enhance the activity of beta cells as occured due to LDL. This indicates the hypolipidemic effect of the Pen- glibenclamide, resulting in an increased insulin release and tanema vestitum extract in diabetic rabbits. Markku (1995) decreased blood glucose level [24]. [29] reported that glycemic control is the major determinant During the second phase of experiment, diabetes was of total and VLDL triglyceride concentration. During the induced by the intraperitoneal injection of alloxan monohy- present study the glibenclamide also caused significant drate. During this study neither glibenclamide nor extract reduction in cholesterol, triglyceride and LDL. Improved has brought the serum glucose concentrations of alloxan- glycaemia control following sulphonylurea therapy has also induced diabetic rabbits to normal range; the reason may been shown to decrease VDL and total triglyceride levels be short duration of treatment. However, both the gliben- [30]. clamide and extract caused significant reduction in serum In the present research, the plant extract and glibenclam- glucose concentration as compared to diabetic control group ide caused significant increase in serum HDL level. High (P<0.05). The results of this research reflected the beneficial density lipoproteins (HDLs) are very important as they pos- effects of plant extract on the glucose level of diabetic rabbits. sess antiatherosclerotic and anti-inflammatory properties The reduction in glucose level in extract-treated group may [31]. Direct evidence for a protective effect of HDLs in be due to the insulin-like effects of the extract, as insulin atherosclerosis has come from transgenic mice in which high increases glucose uptake by the cells [25]. Reduction in levels of expression of apoprotein A-1 (apoA-1) increased the glucose level of diabetic extract-treated group may also be concentration of HDL and protected mice against diet- due to the renewal of β cells following extract administration. induced atherosclerosis [32]. Epidemiological evidence sug- The renewal of β cells in diabetes has been studied in several gests that increased level of low density lipoprotein (LDL) animal models. It has been suggested that regeneration of and low concentration of high density lipoprotein are associ- islet β cells after the use of drug may be the primary cause ated with atherosclerosis [33]. The extract may cause increase of the recovery of alloxan-induced diabetic animals [26]. in HDL level by inducing ApoA-1 production. Lahoz et al. During the present study the serum levels of cholesterol, (2003) suggested that increase in HDL levels after treatment triglyceride and LDL were significantly elevated in diabetic may be due to the induction of ApoA-1 production [34]. animals. The abnormally high concentration of serum lipids The diabetic rabbits showed elevated levels of serum in diabetes is mainly due to increase in the mobilization of GPT, ALP and bilirubin. The levels of these parameters have free fatty acids from the peripheral fat depots [27]. According been reported to be increased in alloxan-induced diabetic to the Framingham Heart study, dyslipidaemia which can animals [35]. During the present study, there occurred 6 ISRN Pharmacology reduction in the level of SGPT, ALP and bilirubin in the callus extracts of Aegle marmelos in rabbit,” ScienceAsia, vol. extract-treated rabbits. 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